Glucose Control in Acute Myocardial Infarction: A Pilot Randomized Study Controlled by Continuous Glucose Monitoring System Comparing the Use of Insulin Glargine with Standard of Care

Background: This pilot study aimed to verify if glycemic control can be achieved in type 2 diabetes patients after acute myocardial infarction (AMI), using insulin glargine (iGlar) associated with regular insulin (iReg), compared with the standard intensive care unit protocol, which uses continuous insulin intravenous delivery followed by NPH insulin and iReg (St. Care). Patients and Methods: Patients (n = 20) within 24 h of AMI were randomized to iGlar or St. Care. Therapy was guided exclusively by capillary blood glucose (CBG), but glucometric parameters were also analyzed by blinded continuous glucose monitoring system (CGMS). Results: Mean glycemia was 141 +/- 39 mg/dL for St. Care and 132 +/- 42 mg/dL for iGlar by CBG or 138 +/- 35 mg/dL for St. Care and 129 +/- 34 mg/dL for iGlar by CGMS. Percentage of time in range (80-180 mg/dL) by CGMS was 73 +/- 18% for iGlar and 77 +/- 11% for St. Care. No severe hypoglycemia (<= 40 mg/dL) was detected by CBG, but CGMS indicated 11 (St. Care) and seven (iGlar) excursions in four subjects from each group, mostly in sulfonylurea users (six of eight patients). Conclusions: This pilot study suggests that equivalent glycemic control without increase in severe hyperglycemia may be achieved using iGlar with background iReg. Data outputs were controlled by both CBG and CGMS measurements in a real-life setting to ensure reliability. Based on CGMS measurements, there were significant numbers of glycemic excursions outside of the target range. However, this was not detected by CBG. In addition, the data indicate that previous use of sulfonylurea may be a potential major risk factor for severe hypoglycemia irrespective of the type of insulin treatment.

Nitrous oxide emissions from gasohol, ethanol and CNG light duty vehicles

A sample of 21 light duty vehicles powered by Otto cycle engines were tested on a chassis dynamometer to measure the exhaust emissions of nitrous oxide (N2O). The tests were performed at the Vehicle Emission Laboratory of CETESB (Environmental Company of the State of Sao Paulo) using the US-FTP-75 (Federal Test Procedure) driving cycle. The sample tested included passenger cars running on three types of fuels used in Brazil: gasohol, ethanol and CNG. The measurement of N2O was made using two methods: Non Dispersive InfraRed (NDIR) analyzer and Fourier Transform InfraRed spectroscopy (FTIR). Measurements of regulated pollutants were also made in order to establish correlations between N2O and NOx. The average N2O emission factors obtained by the NDIR method was 78 +/- 41 mg.km(-1) for vehicles running with gasohol, 73 +/- 45 mg.km(-1) for ethanol vehicles and 171 +/- 69 mg.km(-1) for CNG vehicles. Seventeen results using the FTIR method were also obtained. For gasohol vehicles the results showed a good agreement between the two methods, with an average emission factor of 68 +/- 41 mg.km(-1). The FTIR measurement results of N2O for ethanol and CNG vehicles were much lower than those obtained by the NDIR method. The emission factors were 17 +/- 10 mg.km(-1) and 33 +/- 17 mg.km(-1), respectively, possibly because of the interference of water vapor (present at a higher concentration in the exhaust gases of these vehicles) on measurements by the NDIR method.

A General Latent Class Model for Performance Evaluation of Diagnostic Tests in the Absence of a Gold Standard: An Application to Chagas Disease

We propose a new general Bayesian latent class model for evaluation of the performance of multiple diagnostic tests in situations in which no gold standard test exists based on a computationally intensive approach. The modeling represents an interesting and suitable alternative to models with complex structures that involve the general case of several conditionally independent diagnostic tests, covariates, and strata with different disease prevalences. The technique of stratifying the population according to different disease prevalence rates does not add further marked complexity to the modeling, but it makes the model more flexible and interpretable. To illustrate the general model proposed, we evaluate the performance of six diagnostic screening tests for Chagas disease considering some epidemiological variables. Serology at the time of donation (negative, positive, inconclusive) was considered as a factor of stratification in the model. The general model with stratification of the population performed better in comparison with its concurrents without stratification. The group formed by the testing laboratory Biomanguinhos FIOCRUZ-kit (c-ELISA and rec-ELISA) is the best option in the confirmation process by presenting false-negative rate of 0.0002% from the serial scheme. We are 100% sure that the donor is healthy when these two tests have negative results and he is chagasic when they have positive results.

Caffeic acid phenethyl ester reduces the activation of the nuclear factor kappa B pathway by high-fat diet-induced obesity in mice

Objective. The aim of this study was to investigate the effect of CAPE on the insulin signaling and inflammatory pathway in the liver of mice with high fat diet induced obesity. Material/Methods. Swiss mice were fed with standard chow or high-fat diet for 12-week. After the eighth week, animals in the HFD group with serum glucose levels higher than 200 mg/dL were divided into two groups, HFD and HFD receiving 30 mg/kg of CAPE for 4 weeks. After 12 weeks, the blood samples could be collected and liver tissue extracted for hormonal and biochemical measurements, and insulin signaling and inflammatory pathway analyzes. Results. The high-fat diet group exhibited more weight gain, glucose intolerance, and hepatic steatosis compared with standard diet group. The CAPE treatment showed improvement in glucose sensitivity characterized by an area under glucose curve similar to the control group in an oral glucose tolerance test Furthermore, CAPE treatment promoted amelioration in hepatic steatosis compared with the high-fat diet group. The increase in glucose sensitivity was associated with the improvement in insulin-stimulated phosphorylation of the insulin receptor substrate-2, followed by an increase in Akt phosphorylation. In addition, it was observed that CAPE reduced the induction of the inflammatory pathway, c-jun-N- terminal kinase, the nuclear factor kappa B, and cyclooxygenase-2 expression, respectively. Conclusions. Overall, these findings indicate that CAPE exhibited anti-inflammatory activity that partly restores normal metabolism, reduces the molecular changes observed in obesity and insulin resistance, and therefore has a potential as a therapeutic agent in obesity. (C) 2012 Elsevier Inc. All rights reserved.

Short communication: Principal components and factor analytic models for test-day milk yield in Brazilian Holstein cattle

A total of 46,089 individual monthly test-day (TD) milk yields (10 test-days), from 7,331 complete first lactations of Holstein cattle were analyzed. A standard multivariate analysis (MV), reduced rank analyses fitting the first 2, 3, and 4 genetic principal components (PC2, PC3, PC4), and analyses that fitted a factor analytic structure considering 2, 3, and 4 factors (FAS2, FAS3, FAS4), were carried out. The models included the random animal genetic effect and fixed effects of the contemporary groups (herd-year-month of test-day), age of cow (linear and quadratic effects), and days in milk (linear effect). The residual covariance matrix was assumed to have full rank. Moreover, 2 random regression models were applied. Variance components were estimated by restricted maximum likelihood method. The heritability estimates ranged from 0.11 to 0.24. The genetic correlation estimates between TD obtained with the PC2 model were higher than those obtained with the MV model, especially on adjacent test-days at the end of lactation close to unity. The results indicate that for the data considered in this study, only 2 principal components are required to summarize the bulk of genetic variation among the 10 traits.

Vehicle emissions and PM2.5 mass concentrations in six Brazilian cities

In Brazil, the principal source of air pollution is the combustion of fuels (ethanol, gasohol, and diesel). In this study, we quantify the contributions that vehicle emissions make to the urban fine particulate matter (PM2.5) mass in six state capitals in Brazil, collecting data for use in a larger project evaluating the impact of air pollution on human health. From winter 2007 to winter 2008, we collected 24-h PM2.5 samples, employing gravimetry to determine PM2.5 mass concentrations; reflectance to quantify black carbon concentrations; X-ray fluorescence to characterize elemental composition; and ion chromatography to determine the composition and concentrations of anions and cations. Mean PM2.5 concentrations in the cities of Sao Paulo, Rio de Janeiro, Belo Horizonte, Curitiba, Porto Alegre, and Recife were 28, 17.2, 14.7, 14.4, 13.4, and 7.3 mu g/m(3), respectively. In Sao Paulo and Rio de Janeiro, black carbon explained approximately 30% of the PM2.5 mass. We used receptor models to identify distinct source-related PM2.5 fractions and correlate those fractions with daily mortality rates. Using specific rotation factor analysis, we identified the following principal contributing factors: soil and crustal material; vehicle emissions and biomass burning (black carbon factor); and fuel oil combustion in industries (sulfur factor). In all six cities, vehicle emissions explained at least 40% of the PM2.5 mass. Elemental composition determination with receptor modeling proved an adequate strategy to identify air pollution sources and to evaluate their short- and long-term effects on human health. Our data could inform decisions regarding environmental policies vis-a-vis health care costs.

Electrophysiological study of hearing in full-term small-for-gestational-age newborns

PURPOSE: To describe the Brainstem Auditory Evoked Potential (BAEP) results of full-term small-for-gestational-age newborns, comparing them to the results of full-term appropriate-for-gestational-age newborns, in order to verify whether the small-for-gestational-age condition is a risk indicator for retrocochlear hearing impairment. METHODS: This multicentric prospective cross-sectional study assessed 86 full-term newborns - 47 small- (Study Group) and 39 appropriate-for-gestational-age (Control Group - of both genders, with ages between 2 and 12 days. Newborns with presence of transient evoked otoacoustic emissions and type A tympanometry were included in the study. Quantitative analysis was based on the mean and standard deviation of the absolute latencies of waves I, III and V and interpeak intervals I-III, III-V and I-V, for each group. For qualitative analysis, the BAEP results were classified as normal or altered by analyzing these data considering the age range of the newborn at the time of testing. RESULTS: In the Study Group, nine of the 18 (38%) subjects with altered BAEP results had the condition of small-for-gestational-age as the only risk factor for hearing impairments. In the Control Group, seven (18%) had altered results. Female subjects from the Study Group tended to present more central alterations. In the Control Group, the male group tended to have more alterations. CONCLUSION: Full-term children born small or appropriate for gestational age might present transitory or permanent central hearing impairments, regardless of the presence of risk indicators.

Retrieval of trace gases vertical profile in the lower atmosphere combining. Differential Optical Absorption Spectroscopy with radiative transfer models

The motivation for the work presented in this thesis is to retrieve profile information for the atmospheric trace constituents nitrogen dioxide (NO2) and ozone (O3) in the lower troposphere from remote sensing measurements. The remote sensing technique used, referred to as Multiple AXis Differential Optical Absorption Spectroscopy (MAX-DOAS), is a recent technique that represents a significant advance on the well-established DOAS, especially for what it concerns the study of tropospheric trace consituents. NO2 is an important trace gas in the lower troposphere due to the fact that it is involved in the production of tropospheric ozone; ozone and nitrogen dioxide are key factors in determining the quality of air with consequences, for example, on human health and the growth of vegetation. To understand the NO2 and ozone chemistry in more detail not only the concentrations at ground but also the acquisition of the vertical distribution is necessary. In fact, the budget of nitrogen oxides and ozone in the atmosphere is determined both by local emissions and non-local chemical and dynamical processes (i.e. diffusion and transport at various scales) that greatly impact on their vertical and temporal distribution: thus a tool to resolve the vertical profile information is really important. Useful measurement techniques for atmospheric trace species should fulfill at least two main requirements. First, they must be sufficiently sensitive to detect the species under consideration at their ambient concentration levels. Second, they must be specific, which means that the results of the measurement of a particular species must be neither positively nor negatively influenced by any other trace species simultaneously present in the probed volume of air. Air monitoring by spectroscopic techniques has proven to be a very useful tool to fulfill these desirable requirements as well as a number of other important properties. During the last decades, many such instruments have been developed which are based on the absorption properties of the constituents in various regions of the electromagnetic spectrum, ranging from the far infrared to the ultraviolet. Among them, Differential Optical Absorption Spectroscopy (DOAS) has played an important role. DOAS is an established remote sensing technique for atmospheric trace gases probing, which identifies and quantifies the trace gases in the atmosphere taking advantage of their molecular absorption structures in the near UV and visible wavelengths of the electromagnetic spectrum (from 0.25 μm to 0.75 μm). Passive DOAS, in particular, can detect the presence of a trace gas in terms of its integrated concentration over the atmospheric path from the sun to the receiver (the so called slant column density). The receiver can be located at ground, as well as on board an aircraft or a satellite platform. Passive DOAS has, therefore, a flexible measurement configuration that allows multiple applications. The ability to properly interpret passive DOAS measurements of atmospheric constituents depends crucially on how well the optical path of light collected by the system is understood. This is because the final product of DOAS is the concentration of a particular species integrated along the path that radiation covers in the atmosphere. This path is not known a priori and can only be evaluated by Radiative Transfer Models (RTMs). These models are used to calculate the so called vertical column density of a given trace gas, which is obtained by dividing the measured slant column density to the so called air mass factor, which is used to quantify the enhancement of the light path length within the absorber layers. In the case of the standard DOAS set-up, in which radiation is collected along the vertical direction (zenith-sky DOAS), calculations of the air mass factor have been made using “simple” single scattering radiative transfer models. This configuration has its highest sensitivity in the stratosphere, in particular during twilight. This is the result of the large enhancement in stratospheric light path at dawn and dusk combined with a relatively short tropospheric path. In order to increase the sensitivity of the instrument towards tropospheric signals, measurements with the telescope pointing the horizon (offaxis DOAS) have to be performed. In this circumstances, the light path in the lower layers can become very long and necessitate the use of radiative transfer models including multiple scattering, the full treatment of atmospheric sphericity and refraction. In this thesis, a recent development in the well-established DOAS technique is described, referred to as Multiple AXis Differential Optical Absorption Spectroscopy (MAX-DOAS). The MAX-DOAS consists in the simultaneous use of several off-axis directions near the horizon: using this configuration, not only the sensitivity to tropospheric trace gases is greatly improved, but vertical profile information can also be retrieved by combining the simultaneous off-axis measurements with sophisticated RTM calculations and inversion techniques. In particular there is a need for a RTM which is capable of dealing with all the processes intervening along the light path, supporting all DOAS geometries used, and treating multiple scattering events with varying phase functions involved. To achieve these multiple goals a statistical approach based on the Monte Carlo technique should be used. A Monte Carlo RTM generates an ensemble of random photon paths between the light source and the detector, and uses these paths to reconstruct a remote sensing measurement. Within the present study, the Monte Carlo radiative transfer model PROMSAR (PROcessing of Multi-Scattered Atmospheric Radiation) has been developed and used to correctly interpret the slant column densities obtained from MAX-DOAS measurements. In order to derive the vertical concentration profile of a trace gas from its slant column measurement, the AMF is only one part in the quantitative retrieval process. One indispensable requirement is a robust approach to invert the measurements and obtain the unknown concentrations, the air mass factors being known. For this purpose, in the present thesis, we have used the Chahine relaxation method. Ground-based Multiple AXis DOAS, combined with appropriate radiative transfer models and inversion techniques, is a promising tool for atmospheric studies in the lower troposphere and boundary layer, including the retrieval of profile information with a good degree of vertical resolution. This thesis has presented an application of this powerful comprehensive tool for the study of a preserved natural Mediterranean area (the Castel Porziano Estate, located 20 km South-West of Rome) where pollution is transported from remote sources. Application of this tool in densely populated or industrial areas is beginning to look particularly fruitful and represents an important subject for future studies.

Development of an experiment for ultrahigh-precision g-factor

Die vorliegende Arbeit befasst sich mit der Entwicklung und dem Aufbau eines Experiments zur hochpräzisen Bestimmung des g-Faktors gebundener Elektronen in hochgeladenen Ionen. Der g-Faktor eines Teilchens ist eine dimensionslose Konstante, die die Stärke der Wechselwirkung mit einem magnetischen Feld beschreibt. Im Falle eines an ein hochgeladenes Ion gebundenen Elektrons, dient es als einer der genausten Tests der Quantenelektrodynamik gebundener Zustande (BS-QED). Die Messung wird in einem dreifach Penning-Fallen System durchgeführt und basiert auf dem kontinuierlichen Stern-Gerlach-Effekt. Der erste Teil dieser Arbeit gibt den aktuellen Wissensstand über magnetische Momente wieder. Der hier gewählte experimentelle Aufbau wird begründet. Anschließend werden die experimentellen Anforderungen und die verwendeten Messtechniken erläutert. Das Ladungsbrüten der Ionen - einer der wichtigsten Aufgaben dieser Arbeit - ist dargestellt. Seine Realisierung basiert auf einer Feld-Emissions-Spitzen-Anordnung, die die Messung des Wirkungsquerschnitts für Elektronenstoßionisation ermöglicht. Der letzte Teil der Arbeit widmet sich der Entwicklung und dem Aufbau des Penning-Fallen Systems, sowie der Implementierung des Nachweisprozesses. Gegenwärtig ist der Aufbau zur Erzeugung hochgeladener Ionen und der dazugehörigen Messung des g-Faktors abgeschlossen, einschließlich des Steuerprogramms für die erste Datennahme. Die Ionenerzeugung und das Ladungsbrüten werden die nächsten Schritte sein.

Measurement of the elastic electron-proton cross section and separation of the electric and magnetic form factor in the Q 2 range from 0.004 to 1 (GeV/c) 2

The electromagnetic form factors of the proton are fundamental quantities sensitive to the distribution of charge and magnetization inside the proton. Precise knowledge of the form factors, in particular of the charge and magnetization radii provide strong tests for theory in the non-perturbative regime of QCD. However, the existing data at Q^2 below 1 (GeV/c)^2 are not precise enough for a hard test of theoretical predictions.rnrnFor a more precise determination of the form factors, within this work more than 1400 cross sections of the reaction H(e,e′)p were measured at the Mainz Microtron MAMI using the 3-spectrometer-facility of the A1-collaboration. The data were taken in three periods in the years 2006 and 2007 using beam energies of 180, 315, 450, 585, 720 and 855 MeV. They cover the Q^2 region from 0.004 to 1 (GeV/c)^2 with counting rate uncertainties below 0.2% for most of the data points. The relative luminosity of the measurements was determined using one of the spectrometers as a luminosity monitor. The overlapping acceptances of the measurements maximize the internal redundancy of the data and allow, together with several additions to the standard experimental setup, for tight control of systematic uncertainties.rnTo account for the radiative processes, an event generator was developed and implemented in the simulation package of the analysis software which works without peaking approximation by explicitly calculating the Bethe-Heitler and Born Feynman diagrams for each event.rnTo separate the form factors and to determine the radii, the data were analyzed by fitting a wide selection of form factor models directly to the measured cross sections. These fits also determined the absolute normalization of the different data subsets. The validity of this method was tested with extensive simulations. The results were compared to an extraction via the standard Rosenbluth technique.rnrnThe dip structure in G_E that was seen in the analysis of the previous world data shows up in a modified form. When compared to the standard-dipole form factor as a smooth curve, the extracted G_E exhibits a strong change of the slope around 0.1 (GeV/c)^2, and in the magnetic form factor a dip around 0.2 (GeV/c)^2 is found. This may be taken as indications for a pion cloud. For higher Q^2, the fits yield larger values for G_M than previous measurements, in agreement with form factor ratios from recent precise polarized measurements in the Q2 region up to 0.6 (GeV/c)^2.rnrnThe charge and magnetic rms radii are determined as rn⟨r_e⟩=0.879 ± 0.005(stat.) ± 0.004(syst.) ± 0.002(model) ± 0.004(group) fm,rn⟨r_m⟩=0.777 ± 0.013(stat.) ± 0.009(syst.) ± 0.005(model) ± 0.002(group) fm.rnThis charge radius is significantly larger than theoretical predictions and than the radius of the standard dipole. However, it is in agreement with earlier results measured at the Mainz linear accelerator and with determinations from Hydrogen Lamb shift measurements. The extracted magnetic radius is smaller than previous determinations and than the standard-dipole value.

Role of hypoxia and growth and differentiation factor-5 on differentiation of human mesenchymal stem cells towards intervertebral nucleus pulposus-like cells

There is evidence that mesenchymal stem cells (MSCs) can differentiate towards an intervertebral disc (IVD)-like phenotype. We compared the standard chondrogenic protocol using transforming growth factor beta-1 (TGFß) to the effects of hypoxia, growth and differentiation factor-5 (GDF5), and coculture with bovine nucleus pulposus cells (bNPC). The efficacy of molecules recently discovered as possible nucleus pulposus (NP) markers to differentiate between chondrogenic and IVD-like differentiation was evaluated. MSCs were isolated from human bone marrow and encapsulated in alginate beads. Beads were cultured in DMEM (control) supplemented with TGFß or GDF5 or under indirect coculture with bNPC. All groups were incubated at low (2 %) or normal (20 %) oxygen tension for 28 days. Hypoxia increased aggrecan and collagen II gene expression in all groups. The hypoxic GDF5 and TGFß groups demonstrated most increased aggrecan and collagen II mRNA levels and glycosaminoglycan accumulation. Collagen I and X were most up-regulated in the TGFß groups. From the NP markers, cytokeratin-19 was expressed to highest extent in the hypoxic GDF5 groups; lowest expression was observed in the TGFß group. Levels of forkhead box F1 were down-regulated by TGFß and up-regulated by coculture with bNPC. Carbonic anhydrase 12 was also down-regulated in the TGFß group and showed highest expression in the GDF5 group cocultured with bNPC under hypoxia. Trends in gene expression regulation were confirmed on the protein level using immunohistochemistry. We conclude that hypoxia and GDF5 may be suitable for directing MSCs towards the IVD-like phenotype.

German validation of the Conners Adult ADHD Rating Scales–self-report (CAARS-S) I: Factor structure and normative data

Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. Instruments for diagnosing ADHD in childhood are well validated and reliable, but diagnosis of ADHD in adults remains problematic. Attempts have been made to develop criteria specific for adult ADHD, resulting in the development of self-report and observer-rated questionnaires. To date, the Conners Adult ADHD Rating Scales (CAARS) are the international standard for questionnaire assessment of ADHD. The current study evaluates a German version of the CAARS self-report (CAARS-S).

Leukocyte- and Platelet-Rich Fibrin (L-PRF) for Long-Term Delivery of Growth Factor in Rotator Cuff Repair: Review, Preliminary Results and Future Directions

Surgical repair of the rotator cuff repair is one of the most common procedures in orthopedic surgery. Despite it being the focus of much research, the physiological tendon-bone insertion is not recreated following repair and there is an anatomic non-healing rate of up to 94%. During the healing phase, several growth factors are upregulated that induce cellular proliferation and matrix deposition. Subsequently, this provisional matrix is replaced by the definitive matrix. Leukocyte- and platelet-rich fibrin (L-PRF) contain growth factors and has a stable dense fibrin matrix. Therefore, use of LPRF in rotator cuff repair is theoretically attractive. The aim of the present study was to determine 1) the optimal protocol to achieve the highest leukocyte content; 2) whether L-PRF releases growth factors in a sustained manner over 28 days; 3) whether standard/gelatinous or dry/compressed matrix preparation methods result in higher growth factor concentrations. 1) The standard L-PRF centrifugation protocol with 400 x g showed the highest concentration of platelets and leukocytes. 2) The L-PRF clots cultured in medium showed a continuous slow release with an increase in the absolute release of growth factors TGF-β1, VEGF and MPO in the first 7 days, and for IGF1, PDGF-AB and platelet activity (PF4=CXCL4) in the first 8 hours, followed by a decrease to close to zero at 28 days. Significantly higher levels of growth factor were expressed relative to the control values of normal blood at each culture time point. 3) Except for MPO and the TGFβ-1, there was always a tendency towards higher release of growth factors (i.e., CXCL4, IGF-1, PDGF-AB, and VEGF) in the standard/gelatinous- compared to the dry/compressed group. L-PRF in its optimal standard/gelatinous-type matrix can store and deliver locally specific healing growth factors for up to 28 days and may be a useful adjunct in rotator cuff repair.

Targeting the insulin-like growth factor-1 receptor in human cancer

The insulin-like growth factor (IGF) signaling system plays a crucial role in human cancer and the IGF-1 receptor (IGF-1R) is an attractive drug target against which a variety of novel anti-tumor agents are being developed. Deregulation of the IGF signaling pathway frequently occurs in human cancer and involves the establishment of autocrine loops comprising IGF-1 or IGF-2 and/or IGF-1R over-expression. Epidemiologic studies have documented a link between elevated IGF levels and the development of solid tumors, such as breast, colon, and prostate cancer. Anti-cancer strategies targeting the IGF signaling system involve two main approaches, namely neutralizing antibodies and small molecule inhibitors of the IGF-1R kinase activity. There are numerous reports describing anti-tumor activity of these agents in pre-clinical models of major human cancers. In addition, multiple clinical trials have started to evaluate the safety and efficacy of selected IGF-1R inhibitors, in combination with standard chemotherapeutic regimens or other targeted agents in cancer patients. In this mini review, I will discuss the role of the IGF signaling system in human cancer and the main strategies which have been so far evaluated to target the IGF-1R.

A pain assessment scale for population-based studies: Development and validation of the Pain Module of the Standard Evaluation Questionnaire

The objectives of this study were to develop and validate a tool for assessing pain in population-based observational studies and to develop three subscales for back/neck, upper extremity and lower extremity pain. Based on a literature review, items were extracted from validated questionnaires and reviewed by an expert panel. The initial questionnaire consisted of a pain manikin and 34 items relating to (i) intensity of pain in different body regions (7 items), (ii) pain during activities of daily living (18 items) and (iii) various pain modalities (9 items). Psychometric validation of the initial questionnaire was performed in a random sample of the German-speaking Swiss population. Analyses included tests for reliability, correlation analysis, principal components factor analysis, tests for internal consistency and validity. Overall, 16,634 of 23,763 eligible individuals participated (70%). Test-retest reliability coefficients ranged from 0.32 to 0.97, but only three coefficients were below 0.60. Subscales were constructed combining four items for each of the subscales. Item-total coefficients ranged from 0.76 to 0.86 and Cronbach's alpha were 0.75 or higher for all subscales. Correlation coefficients between subscales and three validated instruments (WOMAC, SPADI and Oswestry) ranged from 0.62 to 0.79. The final Pain Standard Evaluation Questionnaire (SEQ Pain) included 28 items and the pain manikin and accounted for the multidimensionality of pain by assessing pain location and intensity, pain during activity, triggers and time of onset of pain and frequency of pain medication. It was found to be reliable and valid for the assessment of pain in population-based observational studies.